The Road to Cancer Treatment Through Clinical Trials

In 1947, children who developed acute lymphocytic leukemia died. Dr. Sidney Farber, a pathologist at Boston Children’s Hospital, was so distressed doing autopsies on these children that he moved into the clinic and, against the advice of more conservative colleagues, began treating children with aminopterin, a highly toxic drug that starved their cancerous white blood cells of critical nutrients.

Miraculously, for many the disease went into remission, only to recur months later. But Dr. Farber’s last-ditch attempt to save these children began an era of ultimately remarkable progress — decades of clinical trials of progressively complex treatments that now cure nearly 90 percent of children with leukemia.

Olivia Blair of Baltimore, who will be 3 in May, is showing the benefits of this progress. After her T-cell acute lymphocytic leukemia was diagnosed when she was 17 months old, Olivia has weathered more than a year of treatment at Johns Hopkins Kimmel Comprehensive Cancer Center with about 15 different drugs plus radiation to her brain and spine.

With her disease undetectable months later, she is now in a study of an experimental drug to help maintain the remission and is back to a near-normal childhood, a thriving, happy toddler who plays with other children, goes to day care and accompanies her mother grocery shopping.

Kelly Blair, Olivia’s mother, said, “It was very hard for us to decide to participate in the new study, but we finally thought that even if it didn’t help Olivia, it’s going to help other kids.”

The tortuous road to the kind of treatments now saving more than half of all cancer patients is graphically depicted in a six-hour series, “Cancer: The Emperor of All Maladies,” produced by Ken Burns, to be broadcast on public television (PBS) March 30, March 31 and April 1.

The series is based on a Pulitzer Prize-winning book, “The Emperor of All Maladies: A Biography of Cancer,” by an oncologist, Dr. Siddhartha Mukherjee, who provides telling commentary throughout.

“The outcome in children is so stunning because 80 to 90 percent of young patients participate in clinical trials,” Dr. Mukherjee, of Columbia University, said in an interview. “Every trial taught doctors something that led to further trials and better results.”

But only about 5 percent of adults with cancer enter a clinical trial. “That’s not nearly enough to move cancer medicine forward,” he said. “No matter what you do in the lab or in basic science, the ultimate proof of which cancer medicines work comes from clinical trials.”

Although the backbone of today’s successful cancer treatments, clinical trials are poorly understood by the public, often viewed as treating people like guinea pigs instead of as giving them the best chance for survival.

Those who participate are randomly assigned to receive the innovative treatment being studied or the current standard of care. Through such trials, for example, highly disfiguring radical mastectomies for breast cancer have yielded to simple mastectomies or lumpectomies, typically followed by radiation and chemotherapy, with less trauma and far better survival rates.

Even metastatic cancer that has spread now sometimes yields to treatments being tested in clinical trials.

Doug Rogers of Lexington, N.C., was 58 in 2011 when he was found to have melanoma that, despite the best available chemotherapy, had spread throughout his leg and adjacent lymph nodes. He then went to the National Cancer Institute, where Dr. Steven Rosenberg and colleagues are testing an immunological remedy in which the patient’s own cancer-fighting T-cells are harvested, grown in a lab to billions strong and then given back to the patient.

Mr. Rogers, who is also featured in the TV series, said that repeated scans had shown no spread of his cancer and that he was “back to doing almost everything a 62-year-old man can do.”

Although it was once challenging to locate and join a clinical trial, patients and families can now easily find studies and determine eligibility without a doctor as intermediary. The Stand Up to Cancer website offers free information about and access to about 7,000 cancer trials in the United States and Canada. Or you can call the American Association for Cancer Research at 1-877-769-4829.

The American Cancer Society, at cancer.org/clinicaltrials, maintains a clinical trials matching service that is also free and can help locate studies most appropriate to a patient’s medical and personal circumstances. And at www.cancer.gov/clinicaltrials, the National Cancer Institute offers up-to-date descriptions of more than 12,000 trials currently accepting participants, as well as recent trial results by type of cancer, the costs involved and questions to ask about participation. The institute also has a 10-step guide to finding a cancer trial.

The best time to explore participation in a clinical trial is often right after a cancer diagnosis and before receiving any treatment. Some trials won’t accept patients who have already been treated, and sometimes the best chance for success lies in getting the most effective treatment first. However, there are also trials for patients already treated elsewhere without success.

Dr. Mukherjee recommends asking about a trial’s aim. Is it to test safety or effectiveness of a treatment? Why is the trial being done? What were the data that led to the trial in the first place?

“Knowing the answers to such questions allows people to manage their hopes,” he said. “If patients go into a trial with the wrong expectations, they can set themselves up for disappointment.”

Dr. Wendy Schlessel Harpham of Dallas, whose non-Hodgkin’s lymphoma was diagnosed in 1990, is today a highly productive author and speaker because she participated in early trials of rituximab, a monoclonal antibody. Despite intensive chemotherapy and radiation, her disease recurred and, with no other good options, she entered three successive trials that tested rituximab first for safety, then effectiveness.

She had further recurrences, all treated with rituximab, which was approved in 1997. With her last recurrence in 2007, she is now enjoying her longest remission and credits the trials with enabling her to see her three children grow up.